Cefdinir of Formula II is an oral, semi-synthetic cephalosporin antibiotic characterized by having a broad spectrum of antibacterial activity particularly against Staphylococci and Streptococci and a high stability against various β-lactamases. It further exhibits an enhanced activity against gram-positive bacteria as well and is chemically known as 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxyiminoacetamido]-3-vinyl3-cephem-4-carboxylic acid.

Several synthetic methods are known in literature for preparation of cefdinir. For example, U.S. Pat. No. 4,559,334 describes a synthetic method starting from benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylate which is reacted with 4-bromoacetoacetyl bromide, the resulting product is nitrosated to oxime and cyclized to obtain protected cefdinir. Deprotection yielded cefdinir (Refer Scheme-1). However, this synthetic method suffers from several disadvantages such as use of not so easily available raw materials, low yielding steps and isolation involving chromatography and lyophilisation. Overall yield reported is 10–11%.
Ph: Phenyl
Spanish Patent ES 2 013 828 describes alternate route to prepare Cefdinir overcoming the difficulties in U.S. Pat. No. 4,559,334 (Refer Scheme-2).
Thus, (Z)-2-(2-amino-4-thiazolyl)-2-acetyloxyiminoacetic acid was prepared and converted into corresponding acid chloride hydrochloride (A) via reaction with phosphorus pentachloride and condensed with 7-amino-3-vinyl-3-cephem-4-carboxylic acid to yield O-acetyl Cefdinir which was deprotected to yield Cefdinir.

However, in our hands the preparation of (Z)-2-(2-amino-4-thiazolyl)-2-acteyloxyiminoacetylchloride hydrochloride did not prove to be consistent, possibly due to nature of side chain sodium salt and a lot of impurity formation was observed. Moreover this reaction resulted in incomplete conversion and formation of anti-isomer was also observed. Further, this process requires very low temperature leading to additional burden on equipment.
U.S. Pat. No. 6,093,814 describes a process wherein tritylated cefdinir is prepared and isolated as O-trityl cefdinir.p-toluenesulfonic acid.2N,N-dimethylacetamide solvate and further converted into cefdinir either by treatment with formic acid or trifluoroacetic acid (Refer Scheme-3). The disadvantages of this process are use of ethers to isolate O-trityl cefdinir.p-toluenesulfonic acid.2N,N-dimethylacetamide solvate which greatly enhances danger of fire hazard on a commercial scale and poor solvent recovery. Further, we could not realize the specified yields in detritylation step.

Detritylation to obtain cefdinir by using a perhalogenated acids has been described by Otsuka Chemical Company in EP 1 273 587 A1. However, this process also gave low yields and further handling and disposal of perhalogenated acids poses an industrial hazard.
Thus, it is evident that the intermediates described in the prior art to prepare Cefdinir include an acid chloride, a reactive thiophosphate, a reactive ester and the like. However, these intermediates have some disadvantages such as low yields, expensive input raw materials and handling problem in commercial production. Hence, there is a need to use such acylating agent which is capable of transferring the 2-aminothiazolyl moiety to 7-amino-3-cephem compound in good yield without producing any side product and without requiring complicated protection/deprotection operations.